P1063: A SINGLE CENTER EXPERIENCE OF DIAGNOSTICS AND TREATMENT OF RARE MYELOID/LYMPHOID NEOPLASMS WITH PDGFRB GENE REARRANGEMENT
Authors: Irina Nemchenko, Nikolay Tsyba, Ekaterina Chelysheva, Anait Melikyan, Alla Kovrigina, Tatiana Obukhova, Anna Turkina
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: A clonal nature of hypereosinophilic syndromes (HES) is rarely confirmed (about 10%). Rearrangements of the PDGFRB gene in patients (pts) with HES are observed only in about 15% of those cases while PDGFRA markers are found in 70%. The combination of both genes anomalies is not observed. More than 30 partner genes of PDGFRB fusion gene and various chromosomal aberrations have been described. The most frequent is ETV6::PDGFRB fusion gene resulting from t(5;12)(q31-33;p13) translocation. A high sensitivity to targeted therapy with imatinib (IM) is expected. Aims: Summarize a single center data diagnostic and treatment in pts with rare PDGFRB-positive neoplasms. Methods: A total of 126 pts with HES were examined for clonal markers in a period from 2003 to 2021. At the first stage, PDGFRA marker was excluded. Two molecular genetic methods were used to detect PDGFRB gene rearrangements. Before 2014, a qualitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to find ETV6::PDGFRB in 85 pts. Since 2014, fluorescent in situ hybridization (FISH) was used to detect rearrangements of the PDGFRB/5q31-33 gene locus in 41 pts. Median (Me) time to molecular confirmation of diagnosis was 12 months (mo) (2 mo - 22 years). Eight pts received therapy with IM 400 mg QD but one of them (№7, tab. 1) got IM 100 mg QD for the first 4 years. The pt with blast transformation (№1, tab. 1) got IM after achieving BM remission (blasts <5%) on chemotherapy. Me duration of IM use is 25 mo (2-105). Me follow-up for pts with CHR on IM is 48 mo (range 18-105). Results: Involvement of PDGFRB gene was found in 9 pts: 6/41 (14.3%) by FISH, 3/85 (3.5%) by RT-PCR. Me age at diagnosis was 46 years (17-59), male/female=7/2. All pts had typical manifestations of myeloproliferative disease (MPD) with eosinophilia in peripheral blood and/or bone marrow (BM). In patient №1 (tab. 1), 36.9% of myeloid blasts were detected in BM at disease onset. The 5q31-33 anomalies were found in 4/7 pts by a standard cytogenetic assay. In 3 pts the chromosome 5 aberration was cytogenetically cryptic. Complete hematologic response (CHR) was achieved in 5 pts (62.5%). A complete cytogenetic response with disappearance of initial chromosomal aberrations was achieved in 3/3 (100%) pts with CHR after 3 mo of IM treatment. Molecular response (MR) was defined as a negative FISH and RT-PCR (pts №2, №8) and FISH only (pts №1, №7). MR was achieved in 3/4 (75%) pts after 6 (pt №1), 9 (pt №2) and 60 months (№7) on IM. In the last case no MR was achieved after 48 mo on IM 100 mg QD. The IM dose was increased to 400 mg QD and MR was achieved at 9 mo. In case №8 on IM 400 mg QD day the RT-PCR and FISH were positive at mo 2, 6 and 14. After increasing dose to 600 mg QD FISH was negative but RT-PCR was positive at mo 4. Summary/Conclusion: A long-term experience of rare PDGFRB–positive diseases observation reveals that FISH is an optimal method for detection of various PDGFRB gene rearrangements and it should be done in all pts with HES and previously excluded PDGFRA (including those with unchanged karyotype). The IM effectiveness in PDGFRB-positive neoplasms is ambiguous which may be due to the partner gene of PDGFRB. The choice of IM dose should be 400 mg QD. If possible, the molecular response should be assessed by two methods. The PCR method reveals a residual clone with FISH-negativity. An allogeneic stem cell transplantation should be discussed in cases with not sufficient efficacy of IM.Keywords: PDGFRB, Myeloproliferative disorder